Lobular Endocervical Glandular Hyperplasia Research Articles

Management of Incidental Adenoma Malignum of the Cervix: A Case Report

Background: Minimal deviation adenocarcinoma (MDA, also reported as Adenoma Malignum) of the cervix is a rare variant of cervical carcinoma. It is thought to represent about 1% to 3% of all cervical adenocarcinomas. The symptoms can be multifarious and aspecific, however the most peculiar and recurrent is a persistent watery-mucoid vaginal discharge. Because of the symptoms, patients are often referred to a general gynecologist and invariably further examinations are carried out, but not always a precise diagnosis is obtained. Thus, the patients are usually candidated for a surgical non-conservative treatment, mainly to relief the symptoms. Albeit its rareity this cancer is highly aggressive, hence the need for oncologically appropriate approach. Since extremely low incidence of this cancer the majority of general gynecologist will fail in recognise “hints symptoms” and therefore cannot offer a correct treatment. Case presentation: We present a case of a caucasian patient, aged 45 years old, multipara and with profused watery vaginal discharge since half an year. According to anamnestic fitting, gynecological examinations were negative and a recent pap smear was reported as negative. Ultrasound scans described few cysts compatible with Nabothian cysts within an otherwise normal uterus and cervix. MRI of the pelvis confirmed the presence of the cystic morphology of the cervix. In view of the persistent symptomatology without a raised suspect of malignancy, the patient underwent an extrafascial hysterectomy and consensual bilateral salpingooophorectomy because of her age. Histopathology reported differential diagnosis among lobular endocervical glandular hyperplasia versus adenoma Malignum of the cervix. Patient has been therefore referred to the Gynecological Oncology service at our hospital. Histopathology review confirmed MDA of the cervix with a maximum size of 23 mm, negative margins and without lymph-vascular invasion. Multidisciplinary Tumor Board suggested two equivalent options for appropriate treatment: adjuvant external beam radiotherapy of the pelvis with vaginal brachytherapy versus robotic bilateral parametrectomy and lymphnodal pelvic dissection for a proper staging. Further surgical approach has been performed and histopathology confirmed a stage FIGO Ib1. Patient has been therefore sent for routine follow-up and after 10 months she is cancer free. Conclusion: Referring to tertiary hospitals a rare malignancy as MDA for primary treatment is the best practise. However even in case of incidental finding or misdiagnosis, an early and timely referring can hopefully reduce errors and morbidity in the primary treatment.

Foamy gland changes in gastric-type endocervical neoplasia

Foamy gland (FG) change is a distinctive morphological alteration most widely recognised in adenocarcinomas of the prostate and pancreas, and characterised by cells showing prominent cytoplasmic microvacuolation often with deceptively bland nuclear appearances. To our knowledge, FG alteration has not been described in endocervical neoplasia. We report four patients with gastric-type endocervical neoplasms (3 invasive and 1 in situ) in which FG change was present in 30-80% of the tumour cells. The mean age was 56.5 years (range 45-66 years) and three patients, one of whom also had post-coital bleeding, had atypical glandular cells detected on cervical cytology. Three cases showed a pure gastric phenotype and benign gastric-type changes including pyloric metaplasia, tunnel clusters and/or lobular endocervical glandular hyperplasia were also present. These cases were MUC6 positive and p16 negative on immunohistochemistry while HPV was not detected. One adenocarcinoma showed a mixed histological pattern including usual-type endocervical carcinoma and gastric-type adenocarcinoma: only the latter component expressed MUC6 and this case was p16 and HPV18 positive. This report expands the morphological spectrum exhibited by gastric-type endocervical lesions and the range of anatomical sites in which neoplasms with FG features may be encountered.

Profuse Vaginal Discharge May Equally Suggest Adenoma Malignum and Lobular Endocervical Glandular Hyperplasia (LEGH), But Same Cover, Different Story

Profuse Vaginal Discharge May Equally Suggest Adenoma Malignum and Lobular Endocervical Glandular Hyperplasia (LEGH), But Same Cover, Different Story

A case of gastric-type adenocarcinoma of the uterine cervix associated with lobular endocervical glandular hyperplasia: radiologic–pathologic correlation

Gastric-type adenocarcinoma (GAS) of the uterine cervix is a recently defined subtype of mucinous adenocarcinoma. GAS is proposed to include minimal deviation adenocarcinoma (MDA) as a very well-differentiated form and has been suggested to arise from lobular endocervical glandular hyperplasia (LEGH). We report the magnetic resonance imaging (MRI) findings of a GAS associated with LEGH. On MRI, the LEGH component was detected as multiple cystic lesions arranged in a "cosmos pattern", while the GAS was depicted as a predominantly solid lesion containing obvious adenocarcinoma and MDA components, which appeared as mass-like and infiltrative components, respectively. The GAS exhibited tiny cysts on three-dimensional T2-weighted images, high intensity on diffusion-weighted images mostly due to T2 shine-through effect according to apparent diffusion coefficient (ADC) map, and reticular enhancement on dynamic contrast-enhanced MRI, which reflected numerous dilated glandular structures of the tumor. Low ADC was only observed at the deepest invasion front of the obvious adenocarcinoma component. Our case suggests that the MRI features of GAS vary depending on the tumor's histological components, and it is important to be aware of these imaging features when evaluating LEGH on MRI.

Adenomyomas of the uterine cervix: report of a cohort including endocervical and novel variants [corrected

To report a series of 10 cervical adenomyomas of endocervical type and the first case of a mesonephric adenomyoma. The patients' ages ranged from 30 to 55 years. Most lesions were grossly polypoid; a minority were intramural or exophytic. In six of seven endocervical adenomyomas received in consultation, adenoma malignum was considered. A variety of benign lesions, including lobular endocervical glandular hyperplasia (LEGH), adenofibroma, endocervicosis and tunnel clusters, were also considered. The endocervical adenomyomas consisted of bland mucinous glands, sometimes with focal epithelial metaplasia, within a prominent smooth muscle stroma. There was usually a focal lobular architecture and sometimes papillary infoldings. A characteristic feature was a rim of stroma surrounding glands, surrounded in turn by smooth muscle. Previously undescribed features were 'symplastic-like' smooth muscle, stromal adipose tissue, gland rupture with mucin extravasation, prominent adenofibroma-like areas and surface cervical intraepithelial neoplasia (CIN). Diffuse oestrogen receptor (ER) immunoreactivity was useful in excluding adenoma malignum and LEGH, which are hormone receptor-negative. The mesonephric adenomyoma consisted of a lobular arrangement of mesonephric glands [ER/progesterone receptor (PR)-negative; vimentin and luminal CD10 immunoreactivity] within a smooth muscle stroma. Endocervical and mesonephric adenomyomas are rare lesions which are often misdiagnosed, possibly because of lack of familiarity among pathologists.

Pseudoneoplastic glandular lesions of the uterine cervix: a selective review.

Pseudoneoplastic glandular lesions of the cervix continue to be diagnostically challenging for the surgical pathologist. This review covers a select number of these lesions that may be misinterpreted as premalignant or malignant, with an emphasis on those about which Dr Scully has advanced our knowledge. The topics covered include microglandular hyperplasia, mesonephric hyperplasia, diffuse laminar endocervical glandular hyperplasia, lobular endocervical glandular hyperplasia, and endocervical adenomyoma. The first listed entity has a greater diversity of morphology than the name might imply including, but not limited to solid growth and prominent hyaline stroma. The second entity may be remarkably diffuse within the cervical wall and reasonably result in consideration of diagnoses such as minimal deviation adenocarcinoma (adenoma malignum), but has nonmucinous epithelium and bland cytology. The third entity, one of the least common of those considered, represents a peculiar form of reactive hyperplasia of the endocervical epithelium. The fourth entity is the one about which knowledge is still fast advancing. In pure form with no atypia it is almost certainly a clinically benign process, but a subset of cases show cytologic atypia and an occasional association with adenocarcinoma is seen. Finally, adenomyomas of the uterus in general have received much attention in recent years, mostly in the corpus, but the less common endocervical variant may be particularly problematic because mucinous epithelium in abundant myogenic stroma may be potentially confused with an infiltrating differentiated mucinous adenocarcinoma. Although immunohistochemistry may play a role on occasion in evaluating benign endocervical glandular proliferations the mainstay of their interpretation remains conventional morphologic analysis of routinely stained slides.

Forkhead box protein P1 is a useful marker for the diagnosis of mucinous minimal deviation adenocarcinoma of uterine cervix.

Mucinous minimal deviation adenocarcinoma (MDA) is a rare highly differentiated tumor of uterine cervix, of which the confusing histopathology resembling some benign lesions usually makes difficulty for pathologic diagnosis. The expression of forkhead box protein P1 (FOXP1) is found in some kinds of human tumors and is considered to be associated with the progression of the tumors. The purpose of this study is to detect the FOXP1 expression in MDA and evaluate its possible role in the diagnosis of MDA. Twenty-two MDA cases and 20 control cases consisting of 10 cases of lobular endocervical glandular hyperplasia and 10 cases of normal endocervical tissue were included in this study. All available clinical data were collected and immunostaining for FOXP1, carcinoembryonic antigen (CEA), human milk fat globule antigen 1 (HMFG1), estrogen receptor, and progesterone receptor were performed on these cases. The nuclear/cytoplasmic expression of FOXP1 was found in 18 of 22 MDA cases while in 1 of 20 control cases, which showed statistical significance (P = .000). The cytoplasmic CEA expression was found in 14 of 22 MDA cases and 2 of 20 control cases (P = .000), whereas cytoplasmic HMFG1 expression was found in 10 of 22 MDA cases and 4 of 20 control cases (P = .081). No statistical difference was found between FOXP1 and CEA expression (P = .083) or between FOXP1 and HMFG1 expression (P = .375) in MDA. Neither estrogen receptor nor PR expression was found in MDA. The significant expression of FOXP1 in MDA may be helpful to some extent in the pathologic diagnosis of cervical MDA. A widened observation range and further researches are needed to elucidate the potential mechanism.

Lobular endocervical glandular hyperplasia を伴うadenocarcinoma <i>in situ</i> および子宮体癌を認めた重複癌の 1 例

背景 : Lobular endocervical glandular hyperplasia (LEGH) を伴う adenocarcinoma in situ (AIS) および子宮体癌の共存を認めた重複癌の 1 例を経験したので報告する.症例 : 53 歳, 女性. 不正出血を主訴に婦人科を受診. 子宮頸部細胞診では平面的なシート状大型集塊で核は偏在, 重積性はなく, 核小体は目立たない細胞質が黄色調に染まる LEGH の細胞像と, 一部に核縁肥厚を認める核異型を示す異型腺細胞や, さらに異型を増した腺癌細胞を認めた. 子宮内膜細胞診では, G1 の類内膜腺癌細胞を認め子宮体癌と診断した. 手術を施行し, 摘出子宮には, 内膜腺に限局する類内膜腺癌, 頸部には嚢胞状に拡張した腺管周囲に集簇する小腺管を認めた. HIK1083 陽性となる LEGH 部と陰性であった異型 LEGH と AIS を認めた. 類内膜腺癌は頸部 LEGH との連続性は認められなかった.結論 : LEGH を伴う AIS および子宮体癌が共存する 1 例を経験した. 体頸部の重複癌であること, および頸部は LEGH を伴う AIS であることを術前細胞診により推定可能であった.

Hereditary gynecological tumors associated with Peutz-Jeghers syndrome (Review)

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study.

Endocervical Glandular Lesions Exhibiting Gastric Differentiation

A variety of benign and malignant endocervical glandular lesions exhibiting gastric differentiation has been described in the past decade that has resulted in the concept of an important category of cervical adenocarcinoma which is unrelated to human papillomavirus (HPV). Both minimal deviation adenocarcinoma (MDA), also known as adenoma malignum, and the benign lesion lobular endocervical glandular hyperplasia (LEGH), have been known for some time to exhibit a gastric phenotype and immunophenotype (HIK1083 and/or MUC6 positive). Accumulated evidence suggests that a subset of LEGH (atypical LEGH) exhibits a degree of cytologic and/or architectural atypia which, in some cases, may be associated with and be a precursor of adenocarcinomas exhibiting gastric differentiation, including MDA. Gastric-type adenocarcinoma (GAS), a recently described subtype of cervical adenocarcinoma, is an emerging clinicopathologic entity. These neoplasms exhibit a spectrum of differentiation, including MDA as its very well-differentiated form, are unrelated to HPV, and exhibit aggressive clinical behavior. It is proposed that a LEGH-GAS sequence exists and, from a practical point of view, the development of optimal biomarkers is awaited to assist in early detection of GAS and atypical LEGH, as current HPV-targeted screening generally does not detect these lesions and strategies employing HPV vaccination will not prevent their occurrence. Pathologists should be familiar with the morphologic spectrum of these benign, premalignant, and malignant cervical glandular lesions exhibiting gastric differentiation. They are occasionally associated with Peutz-Jeghers syndrome or are a component of "synchronous mucinous metaplasia and neoplasia of the female genital tract."

Clonality analysis suggests that STK11 gene mutations are involved in progression of lobular endocervical glandular hyperplasia (LEGH) to minimal deviation adenocarcinoma (MDA)

Lobular endocervical glandular hyperplasia (LEGH) is a benign proliferative disease of cervical glands. Although histological resemblance of minimal deviation adenocarcinoma (MDA) to LEGH and frequent association of LEGH with MDA have been reported, it still remains unclear whether LEGH is a precancerous lesion of MDA. The present study was undertaken to examine the pathogenetic relationship between LEGH and MDA using a clonality analysis and mutational analyses of the STK11 gene, of which mutations have been reported in MDA. Of nine cases of LEGH only, four were polyclonal and five were monoclonal in composition. Of six LEGH lesions associated with MDA or adenocarcinoma, two were polyclonal and four were monoclonal. In cases of MDA or adenocarcinoma coexisting with LEGH, the patterns of X chromosome inactivation in malignant lesions were identical to those in coexisting LEGH lesions. A mutation of STK11 was only identified in one MDA, but not in LEGH. These results indicate that a subset of LEGH may be a precursor to malignant tumors including MDA and that a mutation of STK11 may be involved in progression of LEGH to MDA.

Premalignant lesions of the lower female genital tract: cervix, vagina and vulva

Premalignant lesions of the lower female genital tract encompassing the cervix, vagina and vulva are variably common and many, but by no means all, are related to infection by human papillomavirus (HPV). In this review, pathological aspects of the various premalignant lesions are discussed, mainly concentrating on new developments. The value of ancillary studies, mainly immunohistochemical, is discussed at the appropriate points. In the cervix, the terminology and morphological features of premalignant glandular lesions is covered, as is the distinction between adenocarcinoma in situ (AIS) and early invasive adenocarcinoma, which may be very problematic. A spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation is emerging with lobular endocervical glandular hyperplasia (LEGH), including so-called atypical LEGH, representing a possible precursor of non HPV-related cervical adenocarcinomas exhibiting gastric differentiation; these include the cytologically bland adenoma malignum and the morphologically malignant gastric type adenocarcinoma. Stratified mucin producing intraepithelial lesion (SMILE) is a premalignant cervical lesion with morphological overlap between cervical intraepithelial neoplasia (CIN) and AIS and which is variably regarded as a form of reserve cell dysplasia or stratified AIS. It is now firmly established that there are two distinct types of vulval intraepithelial neoplasia (VIN) with a different pathogenesis, molecular events, morphological features and risk of progression to squamous carcinoma. These comprise a more common HPV-related usual type VIN (also referred to as classic, undifferentiated, basaloid, warty, Bowenoid type) and a more uncommon differentiated (simplex) type which is non-HPV related and which is sometimes associated with lichen sclerosus. The former has a relatively low risk of progression to HPV-related vulval squamous carcinoma and the latter a high risk of progression to non-HPV related vulval squamous carcinoma. Various aspects of vulval Paget's disease are also discussed.

Carbonic anhydrase type IX expression in lobular endocervical glandular hyperplasia and gastric-type adenocarcinoma of the uterine cervix

The significance of carbonic anhydrase (CA-IX) expression in endocervical glandular lesions was determined to assess the utility of CA-IX immunohistochemistry for the identification of gastric-type endocervical adenocarcinoma and its related lesions. In this study, lobular endocervical glandular hyperplasia (LEGH) (n=5), atypical LEGH (ALEGH) (n=6), and endocervical adenocarcinomas, including usual-type (UEA) (n=6) and gastric-type (GAS) (n=7), were examined by immunohistochemistry for CA-IX expression. The proportion of positive staining and intensity was evaluated as between 0 and 3+. All 13 UEAs and GASs were positive for CA-IX, with 9 cases showing 3+ staining, and 8 cases showing positive areas exceeding 50%. All 11 LEGHs were positive for CA-IX, with all cases showing 50% or more positive areas, although only one case was 3+ positive. Five of 6 ALEGHs were positive for CA-IX, with 4 cases showing 3+ positivity in 100% of the lesion. Non-neoplastic glands were negative for CA-IX, although reserve cell populations and tubal metaplasias were positive for CA-IX. Although CA-IX appears to be involved in tumor progression and may be diagnostically useful in cases of endocervical adenocarcinoma and its precursors, LEGH can be a pitfall, and staining results should be combined with morphology.

Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression: a Gynaecological Oncology Group Study

Background:Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied.Methods:In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16INK4a (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology.Results:Out of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression.Conclusion:Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.

ASGO 2nd International Workshop on Gynecologic Oncology

ASGO 2nd International Workshop on Gynecologic Oncology

Mucinous Epithelial Lesions in Endometrial Curettage Material

To evaluate the immunohistochemical expression of several benign or malignant mucinous lesions that can be encountered in endometrial curettage material. Nineteen well-differentiated mucinous endometrial carcinomas, 12 papillary mucinous metaplasias, 11 cervical microglandular hyperplasias, 11 endocervical adenocarcinomas, 2 goblet cell metaplasias, 1 minimal-deviation adenocarcinoma, and 1 lobular endocervical glandular hyperplasia entered the study. Immunohistochemistry was performed with the following antibodies against: estrogen receptors, progesterone receptors, vimentin, p16, p63, carcinoembryonic antigen, and Ki-67. Immunohistochemistry could easily distinguish endocervical adenocarcinoma of usual type from all other lesions under study. A Vim(-)/p16(-)/p63(high) signature was found to favor a cervical microglandular hyperplasia, whereas both mucinous endometrial carcinoma and mucinous papillary metaplasia would be preferentially characterized by a Vim(+)/p16(+)/p63(low) immunophenotype. A high Ki-67 expression would be of help in differentiating the latter 2 conditions. Statistically, the expression of estrogen receptors, progesterone receptors, and carcinoembryonic antigen did not aid in the differential diagnosis of these 3 conditions. For the 4 cases representing goblet cell metaplasia, minimal-deviation adenocarcinoma and lobular endocervical glandular hyperplasia, no results could be drawn. In endometrial curettage material, the differential diagnosis of lesions comprising mucinous epithelium might be rendered by combining the immunohistochemical expression of vimentin, p16, p63, and Ki-67. Of all lesions, endocervical adenocarcinoma of usual type is the most easily identified.

New developments in endocervical glandular lesions

McCluggage W G (2012) Histopathology New developments in endocervical glandular lesions There is evidence that the prevalence of premalignant and malignant endocervical glandular lesions is increasing in real as well as in apparent terms. In this review, new developments and selected controversial aspects of endocervical glandular lesions are covered, concentrating mainly on premalignant and malignant lesions. The terminology of premalignant endocervical glandular lesions is discussed with a comparison of the World Health Organization classification and the cervical glandular intraepithelial neoplasia (CGIN) system, which is in widespread use in the United Kingdom. Primary cervical adenocarcinomas comprise a heterogeneous group of different morphological types, and while it is known that the majority of these are associated with high-risk human papillomavirus (HPV), it has become clear in recent years that most of the more uncommon morphological types are unassociated with HPV, although they may sometimes be p16-positive. A spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation is now recognized; these include type A tunnel clusters, typical and atypical lobular endocervical glandular hyperplasia, adenoma malignum and gastric-type adenocarcinoma. The latter is a recently described variant of primary cervical adenocarcinoma which has a different morphological appearance to the usual endocervical type and which is probably associated with different patterns of spread and a worse prognosis. There is accumulating evidence that 'early invasive' cervical adenocarcinomas have an excellent prognosis and are suitable for conservative management. Immunohistochemical markers of value in the distinction between a primary cervical and endometrial adenocarcinoma are discussed. While it is well known that a panel of markers comprising oestrogen receptor (ER), vimentin, p16 and monoclonal carcinoembryonic antigen (CEA) is useful, several major pitfalls are pointed out and this panel of markers is predominantly of value in 'low-grade' adenocarcinomas. A related group of lesions, including cervical ectopic prostatic tissue and vaginal tubulosquamous polyp, are probably derived from para-urethral Skene's glands and may be positive with prostatic markers. Recent developments in cervical neuroendocrine neoplasms are discussed, as these are associated not uncommonly with a premalignant or malignant endocervical glandular lesion.

Peutz–Jeghers syndrome-associated atypical mucinous proliferation of the uterine cervix: A case of minimal deviation adenocarcinoma (‘adenoma malignum’) in situ

We describe a case of a non-invasive precursor of minimal deviation adenocarcinoma (MDA) of the uterine cervix, associated with Peutz–Jeghers syndrome (PJS). A 27-year-old woman, who had been followed for PJS, was referred to the gynecology clinic. Colposcopic examination demonstrated a small polypoid lesion in the transformation zone. Microscopic examination of the biopsy specimen demonstrated papillary proliferation of the mucinous epithelium with bland nuclear morphology. Conization revealed lobular endocervical glandular hyperplasia (LEGH) with distinct nuclear anaplasia, as well as papillary proliferation of the mucinous epithelium with mild to moderate nuclear abnormalities. This case suggests that the incipient phase of PJS-associated MDA is related to atypical LEGH (“MDA in situ”), and indicates the importance of early screening and surveillance by gynecologists in cases of PJS to detect cervical adenocarcinomas.

Cancer risk and management in a woman with Peutz-Jeghers syndrome

Peutz-Jeghers syndrome (PJS) is known to cause an elevated risk of cancer development. We present the case of a 41-year-old Japanese woman with PJS who had various lesions in the abdominal and pelvic organs. The preoperative diagnosis was a right ovarian tumor suspected to be a mucinous borderline tumor, a uterine cervical lesion suspected to be lobular endocervical glandular hyperplasia (LEGH), gastrointestinal hamartomatous polyps, and intestinal invagination. She underwent hysterectomy, right salpingo-oophorectomy, left salpingectomy, and partial resection of the jejunum. The pathological diagnosis was an endometriotic cyst of the right ovary, atypical LEGH of the cervix, gastric metaplasia of the fallopian tube, intestinal hamartomatous polyps, and adenocarcinoma in a polyp of the jejunum. This case is representative for women with PJS who may develop multifocal malignancies positively based on the germline mutation of the LKB1/STK11 gene. The cancer risk, surveillance guidelines, and management for women with PJS were discussed in this case conference.

Uterine cervical carcinomas associated with lobular endocervical glandular hyperplasia

To investigate the clinicopathological features of cervical uterine carcinoma associated with lobular endocervical glandular hyperplasia (LEGH). Subjects comprised 12 patients with cervical carcinoma associated with LEGH. Carcinoma included nine invasive adenocarcinomas, two adenocarcinoma in-situ (AIS) and one microinvasive squamous cell carcinoma (SCC). Baseline characteristics, cervical cytology, human papilloma virus (HPV) status, immunohistochemistry, surgical procedures and clinical outcomes were investigated. There was a pair of adenocarcinoma cases in a mother and daughter unrelated to Peutz-Jeghers syndrome. In all patients, atypical cells were seen on cervical cytology (adenocarcinoma cells in 11 cases and SCC cells in one). All the 12 patients were positive for mucin antigen 6 (MUC6) in the LEGH component, while seven patients were positive for gastric mucin (HIK1083). HPV was detected only in the SCC component. One patient with adenocarcinoma stage Ib died of disease 4 years after radical hysterectomy. The others are currently alive 2-16 years postoperatively. The diagnosis of adenocarcinoma with LEGH is not always difficult. The prognosis of adenocarcinoma associated with LEGH may be better than previously expected. Adenocarcinoma with a LEGH component does not always develop into a highly aggressive minimal deviation adenocarcinoma.